Higher organisms undergo several significant transitions during their development. In plants, the best understood of these is the transition from a vegetative to a reproductive phase of shoot development. This transition is preceded by the juvenile-to-adult transition (vegetative phase change), during which the shoot undergoes changes in its vegetative morphology and physiology, and becomes reproductively competent. In contrast to the vegetative-to-reproductive transition, the mechanism of vegetative phase change is very poorly understood. Recent studies indicate that the temporally-regulated miRNA, miR156, plays a major role in this process: miR156 declines in abundance during vegetative phase change, and promotes the expression of the juvenile phase and represses the expression of the adult phase when constitutively expressed. Ten members of the SBP family of transcription factors in Arabidopsis (SPL genes) have target sites for miR156, and we hypothesize that the effect of miR156 on phase change is mediated by some or all of these SPL genes. We propose to 1) determine the developmental functions of these miR156-regulated SPL genes, 2) investigate the organization of the pathways in which miR156 and these SPL genes operate, and 3) identify the factors responsible for the temporal expression of miR156. These experiments will yield the first detailed picture of the molecular mechanism of vegetative phase change and provide significant new information about the regulation and function of small RNAs in plants. PUBLIC HEALTH RELEVANCE: Defects in developmental timing underlie many human diseases and inherited disorders. A better understanding of the fundamental mechanism of developmental timing, and the role of small RNAs in this process, is essential for developing therapies for these problems in human health and development.